Transplant in Rats Cures Disease Blamed for Blindness

By GINA KOLATA

Published: September 25, 1988

Correction Appended

In a major advance, two groups of scientists have successfully transplanted cells from the eye of a rat to the retina of another rat and cured a disease that would otherwise cause blindness. The work, the first successful retinal cell transplant, is the first time that researchers have been able to cure a degenerative disease of the central nervous system.

The researchers cautioned that the studies would have to be duplicated in monkeys and perhaps other animals before the procedure could be tested on people. But they said they were encouraged by the results and estimated that retinal transplants would be possible for people with degenerative eye diseases in 5 to 10 years.

''I'm sure it will eventually be done,'' said Joe G. Hollyfield, a research scientist at Baylor College of Medicine in Houston who specializes in diseases of the retina. ''I'm certain of it.'' A Leading Cause of Blindness

Degenerative diseases of the retina are common, occurring in 400,000 living Americans, according to the Retinitis Pigmentosa Foundation in Baltimore. One of these diseases, macular degeneration, is the leading cause of blindness in this country in people over the age of 60.

Doctors can sometimes slow the loss of vision in patients with degenerative retinal diseases, but they have no way of preventing it. Although many aspects of these diseases are mysteries, scientists suspect that the type of retinal cells transplanted in the recent experiments could save the vision of many patients.

''This is the first time that a degenerative neural disease has been stoppped in its tracks,'' said Matthew LaVail, of the University of California in San Francisco, who studies degenerative diseases of the retina.

The recent experiments, which will be published within a few months in the journal Experimental Eye Research, involve rats with an inherited defect in one type of retinal cell. The defect causes the death of both these cells and others that are nourished and supported by the defective cells. The cell death begins when the rats are about 28 days old. By the time they are 60 days old they are blind.

The retina, at the back of the eye, contains photoreceptor cells. They convert light to electrical signals that are interpreted by the brain.

Covering the photoreceptor cells are the dark brown or black pigmented epithelial cells, which darken the pupil while allowing light to pass through. These cells nourish the photoreceptor cells and also ingest excess segments of photoreceptor cells that develop as these cells grow.

In the diseased rats the pigmented epithelial cells die and the photoreceptor cell membranes start piling up in the animals' eyes as the photoreceptor cells grow. Eventually, the photoreceptor cells die, leaving the animals blind. Healthy Cells Injected

To cure this degenerative disease, James E. Turner and Dr. Linxi Li of Bowman Gray School of Medicine at Wake Forest University in Winston-Salem, N.C., and, independently, Dr. Peter Gouras and his colleagues at Columbia-Prebyterian Medical Center in New York, transplanted healthy pigmented epithelial cells into the animals' eyes by cutting slits in the back of their eyes and injecting tiny drops of fluid containing the healthy cells into the area where the pigmented cells normally grow. The cells survived and thrived and prevented the otherwise inevitable death of photoreceptor cells.

Dr. Turner has operated on more than 200 rats, and, in every case, the transplanted cells survived and prevented photoreceptor cells from dying.

''Turner's work is just phenomenal,'' Dr. LaVail said. ''What he described was so amazing that I went out and visited his lab just to make sure he was not a charlatan. I almost felt it was the high point of my career when I went out there and saw it, it was so phenomenal.''

Dr. LaVail added that he thought the transplanted cells not only survived but also divided and spread in the rats' eyes. ''Not only were the retinas preserved, but I'm positive they were improved,'' he said. ''I honestly think he's getting a much greater distribution than what he's actually injecting. That's how dramatic this whole thing is.''

Dr. Turner said that the cells could have grown or they could simply have spread out, or both. ''There is no answer yet,'' he said.

Dr. Gouras said he and his colleagues hoped to try the retinal cell transplants on monkeys next, and Dr. Turner said he would try them on other species, including rabbits and monkeys, and would try implanting greater numbers of cells in rats.

Experts said that they strongly suspect that many degenerative diseases of the retina that afflict humans also are caused by a deterioration of pigmented epithelial cells of the retina. In particular, they think that these epithelial cells fail in patients with macular degeneration, a disease that mostly afflicts older people and that involves degeneration of the macula, the center of the retina that is responsible for clear vision.

''There are reasons to think and suppose that macular degeneration involves those same cells,'' said Dr. Hollyfield. Dr. Gouras agreed. ''We pretty well know it is caused by a defect in the epithelial cells,'' he said, citing previous research indicating that pathological changes in pigmented retinal epithelial cells that lead to the loss of photoreceptor cells in macular degeneration. Threat of Tissue Rejection

The studies in monkeys and, eventually humans, will have to overcome the problems of tissue rejection, however. The rats were from an inbred strain that accepts each others tissues without any rejection. In patients, the immune system would probably attack and destroy transplanted cells unless immunity were suppressed.

''The problem of rejection may be a major one,'' said Dr. Hollyfield. He added that patients may have to take drugs like, used by patients who receive organ transplants.

He said retinal cells are ''quite hardy'' and should be readily available from eye banks. Also, he said, they can be grown in the laboratory.

He and Dr. LaVail agreed that the surgery was technically difficult but entirely feasible. ''There are many good surgeons who could do this procedure,'' Dr. LaVail said.

The operation would have to be performed before the patients had become blind, but many of the degenerative retinal disease take decades to destroy their victims' vision. Once photoreceptor cells die, however, they cannot be restored.

He predicted that research on retinal cell transplants would now grow explosively. ''I've heard of many many people now who are getting very excited about this,'' he said. ''There will be many studies now that go into different species.''

Correction: October 2, 1988, Sunday, Late City Final Edition A diagram last Sunday with an article about retinal cell transplants in rats labeled layers of the retina incorrectly. The layer next to the outer layer, or sclera, is the choroid. Next to that is a layer of retinal pigment epithelial cells, then a layer of photoreceptor cells.